Bladder carcinoma is the most common malignancy of the urinary system with a high recurrence rate. As of today, bladder carcinoma does not sufficiently benefit from new therapeutic strategies. The molecularly heterogeneous landscape contributes an enormous challenge in the management of this cancer. Consensus clustering based on gene expression data from muscle-invasive and non-muscle-invasive tumors identified multiple intrinsic molecular subsets of this cancer. In our recent study, we have computed epithelial-mesenchymal transition (EMT) scores of three key bladder cancer subtypes followed by the comparative phosphoproteomics profiling of the molecular subtypes. The most aggressive non-type bladder subtype correlated with a mesenchymal-like phenotype. The improved stratification of the molecular features of these subtypes would provide a new opportunity for a deeper understanding of disease pathogenesis. This review focuses on the concepts of cellular plasticity and heterogeneity in bladder carcinoma. We also raised some of the challenges during the discovery and therapeutic intervention of targeted therapy and its clinical implication.

中文翻译：

---

膀胱癌的肿瘤异质性和表型可塑性

膀胱癌是泌尿系统最常见的恶性肿瘤，复发率高。截至今天，膀胱癌并未充分受益于新的治疗策略。分子异质性景观对这种癌症的管理提出了巨大的挑战。基于来自肌肉浸润性和非肌肉浸润性肿瘤的基因表达数据的共识聚类确定了这种癌症的多个内在分子亚群。在我们最近的研究中，我们计算了三种关键膀胱癌亚型的上皮间质转化 (EMT) 评分，然后对分子亚型进行比较磷酸化蛋白质组学分析。最具攻击性的非类型膀胱亚型与间充质样表型相关。这些亚型分子特征的改进分层将为更深入地了解疾病发病机制提供新的机会。本综述重点介绍膀胱癌中细胞可塑性和异质性的概念。我们也在靶向治疗的发现和治疗干预过程中提出了一些挑战及其临床意义。